What are the etiologies of hyperkalemia?

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From the Guidelines

Hyperkalemia, defined as a serum potassium level above 5.0 mEq/L, is primarily caused by kidney dysfunction, medication effects, and excessive potassium intake, as highlighted in the most recent study 1. The etiologies of hyperkalemia can be broadly categorized into:

  • Kidney dysfunction, which impairs potassium excretion
  • Medication effects, particularly from ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, trimethoprim, and certain immunosuppressants like tacrolimus and cyclosporine
  • Excessive potassium intake from supplements or salt substitutes Other significant causes include:
  • Adrenal insufficiency, reducing aldosterone production
  • Cell breakdown conditions like rhabdomyolysis, tumor lysis syndrome, and severe hemolysis, releasing intracellular potassium
  • Metabolic acidosis, causing potassium shifts out of cells
  • Insulin deficiency
  • Certain genetic disorders like Gordon syndrome
  • Pseudohyperkalemia from hemolysis during blood collection or extreme thrombocytosis The management of hyperkalemia typically involves addressing the underlying cause, restricting dietary potassium, reviewing medications, and in severe cases, administering calcium gluconate for cardiac membrane stabilization, insulin with glucose to shift potassium intracellularly, or sodium polystyrene sulfonate to enhance potassium elimination, as recommended in the latest clinical management guidelines 1. Key considerations in managing hyperkalemia include:
  • Monitoring serum creatinine and potassium levels after initiation of treatment with ACE inhibitors, ARBs, or diuretics
  • Implementing treatment protocols or algorithms for managing hyperkalemia, as highlighted in the REVEAL-ED study 1
  • Using intravenous calcium gluconate, insulin/glucose, inhaled β-agonists, and hemodialysis as treatment options for acute hyperkalemia
  • Promoting K+ excretion through increased distal sodium delivery using oral sodium bicarbonate in patients with concurrent metabolic acidosis.

From the Research

Etiologies of Hyperkalemia

The etiologies of hyperkalemia can be categorized into several groups, including:

  • Drug-induced hyperkalemia: This is the most important cause of increased potassium levels in everyday clinical practice 2. A wide range of drugs can cause hyperkalemia by interfering with potassium homeostasis, either by promoting transcellular potassium shift or by impairing renal potassium excretion.
  • Kidney disease: Decreased renal function is a significant risk factor for hyperkalemia, as the kidneys play a crucial role in regulating potassium levels in the body 3, 4, 5.
  • Hyperglycemia: High blood sugar levels can contribute to hyperkalemia 6.
  • Medication use: Certain medications, such as angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and potassium-sparing diuretics, can increase the risk of hyperkalemia 2, 6, 4.
  • Transcellular shifts: Changes in potassium distribution between cells and the extracellular fluid can lead to hyperkalemia 6.
  • Increased potassium intake: Consuming high amounts of potassium can contribute to hyperkalemia, especially in individuals with impaired renal function 5.
  • Critical illness: Conditions such as acute kidney injury, crush injuries, and massive red blood cell transfusions can result in hyperkalemia 4.

Specific Causes of Hyperkalemia

Some specific causes of hyperkalemia include:

  • Potassium-containing agents: Medications that contain potassium can increase the risk of hyperkalemia 2.
  • Aldosterone antagonists: Drugs that block the action of aldosterone can lead to hyperkalemia 2, 4.
  • Nonsteroidal anti-inflammatory drugs: These medications can impair renal potassium excretion and increase the risk of hyperkalemia 2, 3.
  • Beta-blockers: Certain beta-blockers can contribute to hyperkalemia by reducing renal potassium excretion 2, 3.
  • Calcineurin inhibitors: These medications can increase the risk of hyperkalemia by impairing renal function 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Drug-induced hyperkalemia.

Drug safety, 2014

Research

Hyperkalemia in chronic kidney disease.

Revista da Associacao Medica Brasileira (1992), 2020

Research

Potassium Disorders: Hypokalemia and Hyperkalemia.

American family physician, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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